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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Tom
Lillie
+44 1235644790
enquiries@gwt.bio
Dr
Stefan
Symeonides
+44 131 537 1000
Stefan.Symeonides@ed.ac.uk
Advanced or metastatic solid malignancy
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Cancer is one of the leading causes of death, responsible for 16% of deaths worldwide in 2018.
Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer. Immunotherapy with drugs called checkpoint inhibitors have begun to transform cancer treatment, bringing about significant improvements. However, they have only been proven effective for a small subset of cancers and specific patient groups. Hence, an urgent and significant healthcare need remains to support cancer patients who do not respond to first- generation checkpoint inhibitors.
GRWD5769 is a potential new treatment for advanced or metastatic solid malignancies. GRWD5769 works by stopping an enzyme in the body, called endoplasmic reticulum aminopeptidase 1 (ERAP1), from working. ERAP1 is part of how the body recognizes the presence of a cancer tumour and helps trigger the immune system to fight the cancer. However, in patients with cancer, the immune system cells can become exhausted and no longer work effectively. By blocking ERAP1 it makes the tumour look different to the immune system and so the immune system starts fighting the cancer again. Giving the study drug
intermittently may also help prevent the immune system cells from becoming exhausted. Studies have been conducted in animals which support the use of GRWD5769 in humans for the treatment of advanced solid tumours in a broad range of cancer types. GRWD5769 has the potential of producing clinically meaningful improvements in monotherapy and in combination with therapy like cemiplimab (Libtayo®) by enhancing the antitumour immune response.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria as of 02/12/2024:
1. Provision of written informed consent
2. Male or female, ≥ 18 years of age.
3. An ECOG performance status of 0 or 1
4. Willing to permit access to stored historical tumour tissue and prior tumour radiological assessments and tumour biomarker data (if available).
5. Able to take oral medications and be willing to record daily adherence to the study drug.
6. Female participants must be of non-child-bearing potential, or, if of childbearing potential must have a negative pregnancy tests (as required by protocol), must use a highly effective method of contraception combined with a condom and not donate ova (for the protocol specified period of time).
7. Male participants must use a condom and their female participant must also use a highly effective method of contraception (for the protocol specified period of time). If engaging in sexual intercourse with a female partner who could become pregnant and not donate sperm.
8. Estimated life expectancy of at least 3 months, in the opinion of the PI.
9. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures.
Module 1 (Parts A, B and C) and Module 2 (Parts A and B)
10. Participant has cytologically or histologically confirmed locally advanced or metastatic solid malignancy not considered appropriate for which no standard of care (SoC) therapy is available, (or no SoC therapy exists), or who have been offered and declined SoC therapy, or are intolerant of SoC therapy..
11. Participant has measurable disease per RECIST 1.1/iRECIST.
Module 1 (Part B) and Module 2 (Part B) Only
12. Participant has at least one tumour lesion amenable to serial biopsies and is willing to provide consent for biopsies and has measurable disease per RECIST 1.1/iRECIST, excluding the lesion(s) identified for biopsy.
Module 1 (Part D)
Additional selection criteria for Module 1 Part D will be described in a future protocol amendment.
Module 2 (Part C)
Cohort 1
13. Participants with histologically confirmed persistent, recurrent or metastatic cervical cancer who are not amenable to curative therapy.
14. Participants should have received at least 3 months first line anti-PD(L)-1 maintenance therapy (± bevacizumab) following combination with chemotherapy (± bevacizumab) with initial clinical benefit but who have now progressed.
15. Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI.
Cohort 2
16. Participants with histologically confirmed hepatocellular carcinoma who are not amenable to curative therapy and ineligible for loco-regional therapy.
17. Participants should have received at least 3 months first line anti-PD(L)-1 containing with initial clinical benefit but who have now progressed.
18. Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI.
19. Participant has Child-Pugh score class A liver function.
Cohort 3
20. Participants with cytologically or histologically confirmed advanced, recurrent or metastatic disease, which is not amenable to curative therapy, in up to 5 types of solid tumour with moderate to high median TMB.
21. Participants should have received at least 3 months first line anti-PD(L)-1 either initiated as monotherapy or as maintenance therapy with initial clinical benefit, but who have now progressed.
Participants may enrol in the study immediately following progression on the firs
You may not be able to take part if:
Current exclusion criteria as of 02/12/2024:
1. Prior therapy with an ERAP1 inhibitor.2. Any other malignancy within the past 3 years, with the exception of cervical intraepithelial neoplasia and nonmelanoma skin cancer.3. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 1. Participants with Grade 2 toxicity that is not clinically significant (e.g., alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled.4. Active or documented history of autoimmune disease (within 2 years) requiring systemic immunosuppressive therapy, or participant is immunocompromised for any other reason (as determined by the Investigator).5. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks (if stable and requiring no intervention, the participant can be enrolled in the study).6. Uncontrolled seizures7. Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days.8. Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease, severe Parkinson’s disease, active inflammatory bowel disease) or psychiatric condition.9. Active bleeding diatheses.10. Participant has received an organ transplant.11. Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV). Note: participants with prior hepatitis B or C infection which has been adequately treated (and/or is controlled) are eligible for study participation.12. Participant is breastfeeding or pregnant.13. Receipt of licenced or unlicenced cytotoxic, noncytotoxic or small molecule treatment for the malignancy within 28 days or 5 half-lives, whichever is shorter. Note: CPI therapy is permitted within any timeframe.14. Receipt of oral corticosteroids (at a dose > 10 mg prednisone/day or equivalent) within 14 days (except for subjects receiving corticosteroids for adrenal insufficiency).15. Receipt of St John’s Wort or of another concomitant medication, herbal supplement, or food that is a strong inhibitor or inducer of CYP3A4 enzymes within 14 days.16. Receipt of a blood transfusion (blood or blood products) within 7 days.17. Impaired hepatic or renal function.18. Liver function deteriorating in a manner that would likely make the participant ineligible per protocol specified requirements.19. Other evidence of impaired hepatic synthesis function.20. Inadequate bone marrow reserve or organ function. 21. Any prior history of persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L).22. Cardiac dysfunction or other clinically significant cardiac pathology likely to impair the participants ability to participate in the study. 23. Mean QTcF > 450 ms for males or > 470 ms for females. 24. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG. Controlled atrial fibrillation is permitted.25. Any factor that in the Investigator’s opinion increases the risk of QTc prolongation or arrythmic events.26. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements.27. A history of haemolytic anaemia or marrow aplasia.28. Has received a live-virus vaccination within 28 days. Note: seasonal flu or COVID vaccines that do not contain live virus are permitted.29. History of Grade 3 or 4 pneumonitis or interstitial lung disease within the last 5 years, or other clinically significant pulmonary pathology likely to impair ability to participate in the study.
Module 2 all Parts and Module 1A Crossover Participants Only Only30. Has discontinued a prior checkpoint inhibitor due to toxicity. 31. Hypersensitivity to cemiplimab or any of its excipients, or contraindicated to cemiplimab per approved local labelling.32. Has experienced ≥ Grade 2 immune-mediated AE on this study (applies to crossover participants only).Module 2 Only33. Participant previously discontinued treatment with anti-PD-L1 mAb due to immune related toxicity.
_____
Previous exclusion criteria:
1. Prior therapy with an ERAP1 inhibitor, within any timeframe prior to the first dose of IMP. 2. Any other malignancy not meeting inclusion criterion #1 which has been active or treated within the past 3 years, with the exception of cervical intraepithelial neoplasia and nonmelanoma skin cancer 3. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 3, prior to the day of the first dose of IMP. 4. Active or documented history of autoimmune disease 5. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks before the day of the first dose of IMP (if stable and requiring no intervention, the participant can be enrolled in the study). 6. Uncontrolled seizures 7. Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to the day of first dose of IMP. 8. Severe or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease, severe Parkinson’s disease, active inflammatory bowel disease) or psychiatric condition 9. Active bleeding diatheses 10. Participant has received a renal transplant 11. Active hepatitis B, hepatitis C, Epstein-Barr virus (EBV) or human immunodeficiency virus infection (HIV). 12. Participant is breastfeeding or pregnant. 13. Receipt of cytotoxic treatment for the malignancy within 28 days or 5 half-lives, whichever is longer, prior to the day of first dose of IMP. 14. Receipt of noncytotoxic treatment for the malignancy (including biologics such as ICIs, antibodies, nanoparticles etc.) within 5 half-lives of the drug or 42 days (whichever is longer) prior to the day of first dose of study drug (exception: anti-PD-1 or anti-PD-L1 mAb therapy) 15. Receipt of corticosteroids (at a dose > 10 mg prednisone/day or equivalent) within 14 days prior to the day of the first dose of IMP 16. Receipt of any small-molecule IMP within 28 days or 5 half-lives, whichever is longer, prior to the day of the first dose of IMP 17. Receipt of St John’s Wort within 21 days prior to the day of the first dose of IMP or of another concomitant medication, herbal supplement, or food that is a strong inhibitor or inducer of CYP3A4 enzymes (Section 23.5) within 14 days prior to the day of the first dose of IMP 18. Receipt of a blood transfusion (blood or blood products) within 14 days prior to the day of the first dose of IMP 19. Impaired hepatic or renal function as demonstrated by any of the following laboratory values:19.1. Albumin < 30 g/L19.2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × the upper limit of normal (ULN) (> 5.0 × ULN for participants with liver metastases)19.3. Total bilirubin > 1.5 × ULN19.4. Serum creatinine > 1.5 × ULN.20. Liver function deteriorating in a manner that would likely make the participant meet the AST, ALT, or bilirubin levels specified above prior to the day of the first dose of IMP. 21. Other evidence of impaired hepatic synthesis function. 22. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:22.1. Absolute neutrophil count (ANC) < 1.5 × 10^9/L.22.2.. Platelet count < 100 × 10^9/L.22.3. Haemoglobin < 90 g/L. 23. Any prior history of persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L). 24. Cardiac dysfunction (defined as myocardial infarction within the last 6 months, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias, or left ventricular ejection fraction < 55%). 25. Mean QTcF > 450 ms for males or > 470 ms for females at both Screening and prior to the first dose of IMP (on the day of first dose administration) (the mean of triplicate measurements [within 10 minutes with each reading separated by 1-5 minutes] will be used to determine eligibility).26. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third degree heart block). Controlled atrial fibrillation is permitted.27. Any factor that increases the risk of QTc prolongation or of arrhythmic events (e.g., heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under40 years of age). 28. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements.29. A history of haemolytic anaemia or marrow aplasia.30. Has received a live-virus vaccination within 28 days or less of planned treatment start.Note: seasonal flu or COVID vaccines that do not contain live virus are permitted.
Module 2 Only31. Participant previously discontinued treatment with anti-PD-L1 mAb due to immune related toxicity.
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Dr
Stefan
Symeonides
+44 131 537 1000
Stefan.Symeonides@ed.ac.uk
Dr
Tom
Lillie
+44 1235644790
enquiries@gwt.bio
The study is sponsored by Grey Wolf Therapeutics and funded by Grey Wolf Therapeutics.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 56048
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